Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

Obesity is a chronic low-grade inflammation and a risk factor for diseases such as diabetes， hypertension， dyslipidemia， and malignant tumors， demonstrating an increasingly grim development situation. The nuclear factor-kappa B （NF-κB） signaling pathway is a key signaling pathway involved in the immune response and inflammatory response. In obese individuals， the expression of NF-κB is overactivated， which leads to abnormal inflammatory responses in the body. Therefore， it is expected to alleviate inflammation and treat obesity by regulating the NF-κB signaling pathway， which has been proven effective by a large number of studies. The available studies on the NF-κB signaling pathway mostly focus on tumors， and there is no systematic review of the mechanism of this pathway in mediating obesity and the traditional Chinese medicine （TCM） treatment. We reviewed the research progress in the pathological and physiological processes of obesity mediated by NF-κB signaling pathway and TCM treatment， aiming to give insights into the clinical treatment of obesity with TCM and provide reference targets and research directions for exploring the biological foundations and the development of new TCM preparations.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Renal cell carcinoma(RCC)is the most common type of malignant kidney tumors,originating from re-nal tubular epithelial cells.The primary treatment options for RCC include surgery and targeted therapy.Despite the notable advancements in RCC research,significant challenges persist,including the high risk of metastasis and recur-rence post-surgery,as well as the low sensitivity to radiotherapy and chemotherapy.Ferroptosis,a form of regulated cell death first identified in 2012,has garnered significant attention due to its involvement in several cellular processes,including redox balance,iron metabolism,and various signaling pathways related to cancer progression.Given its po-tential to be modulated,ferroptosis offers significant promise for the treatment of cancers,ischemic organ damage,and other degenerative diseases associated with lipid peroxidation.This review discusses recent developments in ferroptosis research,with a particular focus on its role in RCC,and explores future research directions in this area.

Objective:To investigate changes in behavior and hippocampal and prefrontal cortical myelin basic protein(MBP) in model mice with post-traumatic stress disorder(PTSD).Methods:Thirty-two clean-grade male C57BL/6J mice were randomly divided into control group, PTSD 3 d group, PTSD 7 d group and PTSD 14 d group based on matching body mass, with 8 mice in each group. The mice in PTSD 3 d, 7 d and 14 d groups were decapitated at 3 d, 7 d, and 14 d after modeling.The PTSD mouse model was established through conditioned foot shock and single prolonged stress. Anxious- and depressive-like behaviors of mice were assessed by the open field test(OFT). The mouse step-through passive avoidance experiment was used for electric shock training and learning and memory retention. Myelin morphology alterations in the hippocampus and prefrontal cortex of the mouse were examined via myelin staining.The expression levels of MBP were quantified using Western blot and immunohistochemical staining techniques. All experimental data were analyzed and visualized using GraphPad Prism 8.0.2 and SPSS 25.0, the multi groups comparison of behavioral and molecular indicator data was conducted by one-way ANOVA, and the correlation between MBP relative protein expression level and behavioral indicators was analyzed by Pearson correlation analysis.Results:(1) Behavioral results: in OFT, there were significant differences in total distance, average speed, time of stationary and times of entering the central area among all groups( F=16.72, 16.74, 7.37, 5.93, all P<0.05).The total distance and the average speed time of PTSD 3 d, 7 d, 14 d group were all lower than those in control group(all P<0.05).In the mouse step-through passive avoidance experiment, significant differences were observed across all groups in terms of total distance traveled, average speed, dark box entries, and activity time( F=52.78, 55.47, 9.07, 24.88, all P<0.05).All the indexes of PTSD 3 d group and PTSD 7 d group were all higher than those in control group and PTSD 14 d group(all P<0.05).(2)Myelin staining revealed statistically significant differences in the myelin staining areas of the hippocampal CA1 region and the prefrontal cortex across all groups( F=6.67, 5.77, all P<0.05). The stained myelin area in the CA1 region of the hippocampus in the PTSD 3 d group((123.30±11.62)μm 2)was significantly lower compared to the control group((153.00±2.61)μm 2)( P<0.05). The stained myelin area in the prefrontal cortex of the PTSD 3 d group((119.50±9.26)μm 2)was significantly lower compared to that in the control group((154.80±12.40)μm 2)( P<0.05). (3) Western blot results demonstrated significant variations in the expression levels of myelin basic protein (MBP) within the hippocampus and prefrontal cortex across all experimental groups ( F=10.15, 5.28, all P<0.05). The expression levels of MBP in the hippocampal tissue of the PTSD 3 d group (0.89±0.07), PTSD 7 d group (0.90±0.14), and PTSD 14 d group (0.85±0.13) were significantly lower compared to those in the control group(1.17±0.02)(all P<0.05). The expression levels of MBP protein in the prefrontal cortex of the PTSD 3 d group(0.73±0.16) and PTSD 7 d group (0.70±0.12)were significantly lower compared to those in the control group (0.94±0.04)(all P<0.05). (4) Immunohistochemical staining revealed significant variations in the number of MBP-positive cells within the hippocampal CA1 region and the prefrontal cortex across all groups ( F=39.32, 21.81, both P<0.05). The quantity of MBP-positive cells in the hippocampal tissue of mice in the PTSD 3 d group((187.10±1.12)/mm 2)and PTSD 7 d group((193.10±2.18) /mm 2)was significantly reduced compared to the control group((204.80±3.25)/mm 2)(all P<0.05). The quantity of MBP-positive cells in the prefrontal cortex of the PTSD 7 d group((183.90±1.71)/mm 2) was significantly reduced compared to the control group((191.60±1.04) /mm 2)( P<0.05). Conclusion:The PTSD model mice showed anxious- and depression-like behavior, impaired learning and memory ability, and myelin damage in the hippocampus and prefrontal cortex.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

Objective: To compare the value of a body shape index (ABSI) and body roundness index (BRI) in predicting non-alcoholic fatty liver disease (NAFLD) among non-obese population, so as to provide a reference for the early identification of populations at high risk of NAFLD. Methods: Adults with a body mass index (BMI) of less than 28 kg/m2 who underwent health check-ups in Xiyuan Hospital of China Academy of Chinese Medical Sciences from 2022 to 2024 were selected as the study subjects. Demographic information, disease history, height, weight, waist circumference, blood pressure, and blood lipid indicators were collected, and ABSI and BRI were calculated. NAFLD was diagnosed using abdominal ultrasound. A multivariable logistic regression model was employed to analyze the relationships between ABSI, BRI and NAFLD among non-obese population. A generalized additive model combined with the penalized spline method was used to fit smooth curves to identify nonlinear relationships, and threshold effects were utilized to determine inflection points. The values of ABSI and BRI in predicting NAFLD among non-obese population were used the receiver operating characteristic (ROC) curve. Results: A total of 1 195 individuals were surveyed, including 345 males (28.87%) and 850 females (71.13%). A total of 348 cases of NAFLD were detected among the non-obese population, with a detection rate of 29.12%. The adjusted ABSI (sABSI) in the NAFLD group and non-NAFLD group were 7.95±0.33 and 8.08±0.34, while the BRI were 3.35±0.79 and 4.15±0.64, respectively, with statistically significant differences between the two groups (both P<0.05). Multivariable logistic regression analysis showed that, after adjusting for demographic information, disease history, blood pressure, and blood lipid indicators, both sABSI (OR=1.932, 95%CI: 1.184-3.158) and BRI (OR=1.594, 95%CI: 1.071-2.360) were significantly associated with NAFLD among non-obese population. Nonlinear positive correlations were observed between sABSI, BRI, and NAFLD among non-obese population. When sABSI≤8.46 and BRI≥2.72, both indices were positively associated with NAFLD. The area under the ROC curve for ABSI and BRI in predicting NAFLD risk among non-obese population were 0.619 and 0.782, respectively, with optimal cut-off values of 0.082 and 3.656, respectively. Conclusions ABSI and BRI show a non-linear relationship with NAFLD among non-obese population. BRI demonstrates relatively better performance in predicting NAFLD risk among this population and can serve as an auxiliary indicator for the early identification of NAFLD among non-obese population.